Dose and Duration of Metronidazole and Amoxicillin for Treatment of Chronic Periodontitis

NCT ID: NCT02735395

Last Updated: 2020-01-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

110 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-07-31

Study Completion Date

2020-12-31

Brief Summary

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The aim of this study was to compare the clinical and microbiological outcomes of different dosages of metronidazole (MTZ) and of the duration of the systemic administration of MTZ and amoxicillin as adjunct to scaling and root planing (SRP) in the treatment of generalized chronic periodontitis (GChP).

Detailed Description

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Randomized clinical trials and systematic reviews have shown that the use of the combination of metronidazole (MTZ) and amoxicillin (AMX) significantly improves the benefits of the SRP in the treatment of subjects with periodontitis. However, the optimal dosage and interval of administration of these antibiotics are still unclear. Therefore, the aim of this study was to compare the clinical and microbiological outcomes of different dosages and duration of the systemic administration of the combination of MTZ and AMX as adjunct to scaling and root planing (SRP) in the treatment of generalized chronic periodontitis (GChP). One hundred ten subjects will be randomly assigned to receive SRP plus placebo, or SRP combined with 250 mg or 400 mg of MTZ, plus AMX (500 mg) TID, for either 7 or 14 days. Subjects will be clinically and microbiologically monitored up to 1 year post-therapy.

Conditions

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Chronic Periodontitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Control

Scaling and root planing (SRP) + two placebo pills thrice a day (TID) for 14 days (control group)

Group Type PLACEBO_COMPARATOR

Scaling and root planing (SRP)

Intervention Type PROCEDURE

SRP performed in four to six appointments lasting approximately 1 h each, using manual curettes (Hu-Friedy, Chicago, IL, USA) and ultrasonic device (Cavitron Select SPC, Dentsply professional, York, PA, USA) under local anesthesia. The deep sites will be scaled throughout the first week and treatment of the entire oral cavity will be completed in 14 days.

Placebo 400 (14 days)

Intervention Type OTHER

Subjects will intake placebo of Metronidazole 400 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.

Placebo 500

Intervention Type OTHER

Subjects will intake placebo of Amoxicillin 500 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.

MTZ 250 (7 days)

SRP + MTZ (250mg/TID) + AMX, for 7 days and placebos for another 7 days

Group Type ACTIVE_COMPARATOR

Scaling and root planing (SRP)

Intervention Type PROCEDURE

SRP performed in four to six appointments lasting approximately 1 h each, using manual curettes (Hu-Friedy, Chicago, IL, USA) and ultrasonic device (Cavitron Select SPC, Dentsply professional, York, PA, USA) under local anesthesia. The deep sites will be scaled throughout the first week and treatment of the entire oral cavity will be completed in 14 days.

Metronidazole 250 (7 days)

Intervention Type DRUG

Subjects will intake Metronidazole 250 mg. for 7 days, starting immediately after the first session of Scaling and Root Planing.

Amoxicillin

Intervention Type DRUG

Subjects will intake Amoxicillin 500 mg. for 14 days, starting immediately after and the first session of Scaling and Root Planing.

Placebo 250 (7 days)

Intervention Type OTHER

Subjects will intake placebo of Metronidazole 250 mg. for 7 days, starting immediately after to intake Metronidazole 250 mg.

MTZ 400 (7 days)

SRP + MTZ (400mg/TID) + AMX, for 7 days and placebos for another 7 days

Group Type ACTIVE_COMPARATOR

Scaling and root planing (SRP)

Intervention Type PROCEDURE

SRP performed in four to six appointments lasting approximately 1 h each, using manual curettes (Hu-Friedy, Chicago, IL, USA) and ultrasonic device (Cavitron Select SPC, Dentsply professional, York, PA, USA) under local anesthesia. The deep sites will be scaled throughout the first week and treatment of the entire oral cavity will be completed in 14 days.

Metronidazole 400 (7 days)

Intervention Type DRUG

Subjects will intake Metronidazole 400 mg. for 7 days, starting immediately after the first session of Scaling and Root Planing.

Amoxicillin

Intervention Type DRUG

Subjects will intake Amoxicillin 500 mg. for 14 days, starting immediately after and the first session of Scaling and Root Planing.

Placebo 400 (7 days)

Intervention Type OTHER

Subjects will intake placebo of Metronidazole 400 mg. for 7 days, starting immediately after to intake Metronidazole 400 mg.

MTZ 250 (14 days)

SRP +MTZ (250mg/TID) + AMX for 14 days

Group Type ACTIVE_COMPARATOR

Scaling and root planing (SRP)

Intervention Type PROCEDURE

SRP performed in four to six appointments lasting approximately 1 h each, using manual curettes (Hu-Friedy, Chicago, IL, USA) and ultrasonic device (Cavitron Select SPC, Dentsply professional, York, PA, USA) under local anesthesia. The deep sites will be scaled throughout the first week and treatment of the entire oral cavity will be completed in 14 days.

Metronidazole 250 (14 days)

Intervention Type DRUG

Subjects will intake Metronidazole 250 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.

Amoxicillin

Intervention Type DRUG

Subjects will intake Amoxicillin 500 mg. for 14 days, starting immediately after and the first session of Scaling and Root Planing.

MTZ 400 (14 days)

SRP +MTZ (400mg/TID) + AMX for 14 days

Group Type ACTIVE_COMPARATOR

Scaling and root planing (SRP)

Intervention Type PROCEDURE

SRP performed in four to six appointments lasting approximately 1 h each, using manual curettes (Hu-Friedy, Chicago, IL, USA) and ultrasonic device (Cavitron Select SPC, Dentsply professional, York, PA, USA) under local anesthesia. The deep sites will be scaled throughout the first week and treatment of the entire oral cavity will be completed in 14 days.

Metronidazole 400 (14 days)

Intervention Type DRUG

Subjects will intake Metronidazole 400 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.

Amoxicillin

Intervention Type DRUG

Subjects will intake Amoxicillin 500 mg. for 14 days, starting immediately after and the first session of Scaling and Root Planing.

Interventions

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Scaling and root planing (SRP)

SRP performed in four to six appointments lasting approximately 1 h each, using manual curettes (Hu-Friedy, Chicago, IL, USA) and ultrasonic device (Cavitron Select SPC, Dentsply professional, York, PA, USA) under local anesthesia. The deep sites will be scaled throughout the first week and treatment of the entire oral cavity will be completed in 14 days.

Intervention Type PROCEDURE

Metronidazole 250 (7 days)

Subjects will intake Metronidazole 250 mg. for 7 days, starting immediately after the first session of Scaling and Root Planing.

Intervention Type DRUG

Metronidazole 400 (7 days)

Subjects will intake Metronidazole 400 mg. for 7 days, starting immediately after the first session of Scaling and Root Planing.

Intervention Type DRUG

Metronidazole 250 (14 days)

Subjects will intake Metronidazole 250 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.

Intervention Type DRUG

Metronidazole 400 (14 days)

Subjects will intake Metronidazole 400 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.

Intervention Type DRUG

Amoxicillin

Subjects will intake Amoxicillin 500 mg. for 14 days, starting immediately after and the first session of Scaling and Root Planing.

Intervention Type DRUG

Placebo 250 (7 days)

Subjects will intake placebo of Metronidazole 250 mg. for 7 days, starting immediately after to intake Metronidazole 250 mg.

Intervention Type OTHER

Placebo 400 (7 days)

Subjects will intake placebo of Metronidazole 400 mg. for 7 days, starting immediately after to intake Metronidazole 400 mg.

Intervention Type OTHER

Placebo 400 (14 days)

Subjects will intake placebo of Metronidazole 400 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.

Intervention Type OTHER

Placebo 500

Subjects will intake placebo of Amoxicillin 500 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* ≥30 years of age;
* at least 15 teeth (excluding third molars and teeth with advanced decay indicated for extraction)
* a minimum of 6 teeth with at least one site each with probing depth (PD) and clinical \* attachment level (CAL) ≥5 mm;
* at least 30% of the sites with PD and CAL ≥4 mm and bleeding on probing (BOP).

Exclusion Criteria

* pregnancy
* breastfeeding
* current smoking and former smoking within the past 5 years;
* systemic diseases that could affect the progression of periodontitis (e.g. diabetes, immunological disorders, osteoporosis);
* scaling and root planing an in the previous 12 months;
* antibiotic therapy in the previous 6 months;
* long-term intake of anti-inflammatory medications;
* need for antibiotic pre-medication for routine dental therapy;
* allergy to metronidazole and/or amoxicillin.
Minimum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Guarulhos

OTHER

Sponsor Role lead

Responsible Party

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Belén Retamal-Valdes

DDS, MSc, PhD Student

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Magda Feres, Professor

Role: STUDY_CHAIR

Guarulhos University

Locations

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Guarulhos University

Guarulhos, São Paulo, Brazil

Site Status

Countries

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Brazil

References

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Aimetti M, Romano F, Guzzi N, Carnevale G. Full-mouth disinfection and systemic antimicrobial therapy in generalized aggressive periodontitis: a randomized, placebo-controlled trial. J Clin Periodontol. 2012 Mar;39(3):284-94. doi: 10.1111/j.1600-051X.2011.01795.x. Epub 2012 Jan 4.

Reference Type BACKGROUND
PMID: 22220822 (View on PubMed)

Carvalho LH, D'Avila GB, Leao A, Haffajee AD, Socransky SS, Feres M. Scaling and root planing, systemic metronidazole and professional plaque removal in the treatment of chronic periodontitis in a Brazilian population. I. clinical results. J Clin Periodontol. 2004 Dec;31(12):1070-6. doi: 10.1111/j.1600-051X.2004.00605.x.

Reference Type BACKGROUND
PMID: 15560807 (View on PubMed)

Cionca N, Giannopoulou C, Ugolotti G, Mombelli A. Amoxicillin and metronidazole as an adjunct to full-mouth scaling and root planing of chronic periodontitis. J Periodontol. 2009 Mar;80(3):364-71. doi: 10.1902/jop.2009.080540.

Reference Type BACKGROUND
PMID: 19254119 (View on PubMed)

Feres M, Figueiredo LC, Soares GM, Faveri M. Systemic antibiotics in the treatment of periodontitis. Periodontol 2000. 2015 Feb;67(1):131-86. doi: 10.1111/prd.12075.

Reference Type BACKGROUND
PMID: 25494600 (View on PubMed)

Feres M, Soares GM, Mendes JA, Silva MP, Faveri M, Teles R, Socransky SS, Figueiredo LC. Metronidazole alone or with amoxicillin as adjuncts to non-surgical treatment of chronic periodontitis: a 1-year double-blinded, placebo-controlled, randomized clinical trial. J Clin Periodontol. 2012 Dec;39(12):1149-58. doi: 10.1111/jcpe.12004. Epub 2012 Sep 27.

Reference Type BACKGROUND
PMID: 23016867 (View on PubMed)

Guerrero A, Griffiths GS, Nibali L, Suvan J, Moles DR, Laurell L, Tonetti MS. Adjunctive benefits of systemic amoxicillin and metronidazole in non-surgical treatment of generalized aggressive periodontitis: a randomized placebo-controlled clinical trial. J Clin Periodontol. 2005 Oct;32(10):1096-107. doi: 10.1111/j.1600-051X.2005.00814.x.

Reference Type BACKGROUND
PMID: 16174275 (View on PubMed)

Mestnik MJ, Feres M, Figueiredo LC, Soares G, Teles RP, Fermiano D, Duarte PM, Faveri M. The effects of adjunctive metronidazole plus amoxicillin in the treatment of generalized aggressive periodontitis: a 1-year double-blinded, placebo-controlled, randomized clinical trial. J Clin Periodontol. 2012 Oct;39(10):955-61. doi: 10.1111/j.1600-051X.2012.01932.x. Epub 2012 Aug 6.

Reference Type BACKGROUND
PMID: 22882646 (View on PubMed)

Mestnik MJ, Feres M, Figueiredo LC, Duarte PM, Lira EA, Faveri M. Short-term benefits of the adjunctive use of metronidazole plus amoxicillin in the microbial profile and in the clinical parameters of subjects with generalized aggressive periodontitis. J Clin Periodontol. 2010 Apr;37(4):353-65. doi: 10.1111/j.1600-051X.2010.01538.x.

Reference Type BACKGROUND
PMID: 20447259 (View on PubMed)

Miranda TS, Feres M, Perez-Chaparro PJ, Faveri M, Figueiredo LC, Tamashiro NS, Bastos MF, Duarte PM. Metronidazole and amoxicillin as adjuncts to scaling and root planing for the treatment of type 2 diabetic subjects with periodontitis: 1-year outcomes of a randomized placebo-controlled clinical trial. J Clin Periodontol. 2014 Sep;41(9):890-9. doi: 10.1111/jcpe.12282. Epub 2014 Jul 17.

Reference Type BACKGROUND
PMID: 24930639 (View on PubMed)

Rabelo CC, Feres M, Goncalves C, Figueiredo LC, Faveri M, Tu YK, Chambrone L. Systemic antibiotics in the treatment of aggressive periodontitis. A systematic review and a Bayesian Network meta-analysis. J Clin Periodontol. 2015 Jul;42(7):647-57. doi: 10.1111/jcpe.12427.

Reference Type BACKGROUND
PMID: 26087839 (View on PubMed)

Sgolastra F, Gatto R, Petrucci A, Monaco A. Effectiveness of systemic amoxicillin/metronidazole as adjunctive therapy to scaling and root planing in the treatment of chronic periodontitis: a systematic review and meta-analysis. J Periodontol. 2012 Oct;83(10):1257-69. doi: 10.1902/jop.2012.110625. Epub 2012 Feb 14.

Reference Type BACKGROUND
PMID: 22220767 (View on PubMed)

Sgolastra F, Petrucci A, Gatto R, Monaco A. Effectiveness of systemic amoxicillin/metronidazole as an adjunctive therapy to full-mouth scaling and root planing in the treatment of aggressive periodontitis: a systematic review and meta-analysis. J Periodontol. 2012 Jun;83(6):731-43. doi: 10.1902/jop.2011.110432. Epub 2011 Nov 3.

Reference Type BACKGROUND
PMID: 22050545 (View on PubMed)

Silva MP, Feres M, Sirotto TA, Soares GM, Mendes JA, Faveri M, Figueiredo LC. Clinical and microbiological benefits of metronidazole alone or with amoxicillin as adjuncts in the treatment of chronic periodontitis: a randomized placebo-controlled clinical trial. J Clin Periodontol. 2011 Sep;38(9):828-37. doi: 10.1111/j.1600-051X.2011.01763.x. Epub 2011 Jul 15.

Reference Type BACKGROUND
PMID: 21762197 (View on PubMed)

Zandbergen D, Slot DE, Niederman R, Van der Weijden FA. The concomitant administration of systemic amoxicillin and metronidazole compared to scaling and root planing alone in treating periodontitis: =a systematic review=. BMC Oral Health. 2016 Feb 29;16:27. doi: 10.1186/s12903-015-0123-6.

Reference Type BACKGROUND
PMID: 26928597 (View on PubMed)

Zandbergen D, Slot DE, Cobb CM, Van der Weijden FA. The clinical effect of scaling and root planing and the concomitant administration of systemic amoxicillin and metronidazole: a systematic review. J Periodontol. 2013 Mar;84(3):332-51. doi: 10.1902/jop.2012.120040. Epub 2012 May 21.

Reference Type BACKGROUND
PMID: 22612369 (View on PubMed)

Soares GM, Mendes JA, Silva MP, Faveri M, Teles R, Socransky SS, Wang X, Figueiredo LC, Feres M. Metronidazole alone or with amoxicillin as adjuncts to non-surgical treatment of chronic periodontitis: a secondary analysis of microbiological results from a randomized clinical trial. J Clin Periodontol. 2014 Apr;41(4):366-76. doi: 10.1111/jcpe.12217.

Reference Type BACKGROUND
PMID: 24834504 (View on PubMed)

Khattri S, Kumbargere Nagraj S, Arora A, Eachempati P, Kusum CK, Bhat KG, Johnson TM, Lodi G. Adjunctive systemic antimicrobials for the non-surgical treatment of periodontitis. Cochrane Database Syst Rev. 2020 Nov 16;11(11):CD012568. doi: 10.1002/14651858.CD012568.pub2.

Reference Type DERIVED
PMID: 33197289 (View on PubMed)

Borges I, Faveri M, Figueiredo LC, Duarte PM, Retamal-Valdes B, Montenegro SCL, Feres M. Different antibiotic protocols in the treatment of severe chronic periodontitis: A 1-year randomized trial. J Clin Periodontol. 2017 Aug;44(8):822-832. doi: 10.1111/jcpe.12721. Epub 2017 Jul 26.

Reference Type DERIVED
PMID: 28303587 (View on PubMed)

Other Identifiers

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SISNEP/513

Identifier Type: -

Identifier Source: org_study_id

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